Evaluation of the Therapeutic Potential of Spirulina Polysaccharides on Carbon Tetrachloride-Induced Liver Fibrosis in Mice: A Study Based on the Interaction Between Gut Microbiota and Metabolites

Introduction: Hepatic fibrosis represents a critical intermediate stage in the progression from chronic liver disease to cirrhosis and ultimately hepatocellular carcinoma. Spirulina platensis, a microorganism rich in bioactive compounds, contains several functional components, among which are Spirulina polysaccharides and phycocyanin. Both have been demonstrated to exhibit multiple biological activities, including antioxidant, anti-inflammatory, and immunomodulatory effects. However, the intervention effects and mechanisms of Spirulina polysaccharides and phycocyanin on CCl4-induced hepatic fibrosis remain unclear. 16S rRNA sequencing and non-targeted metabolomics technologies are employed to analyze bacterial taxa and metabolic pathways. Methods: Hepatic fibrosis (HF) was induced in male C57BL/6J mice via intraperitoneal injection of CCl4. After 1 week of modeling, mice were intragastrically administered SPP or PC for 4 consecutive weeks. Gut microbiota composition and fecal metabolites were analyzed using 16S rRNA gene sequencing and metabolomics. Results: SPP showed more pronounced protective effects than PC under the experimental conditions used in this study. SPP treatment significantly alleviated hepatic fibrosis in mice. Compared with the model group, SPP administration markedly increased the abundance of bacterial taxa and modulated fecal metabolic profiles, including short-chain fatty acid metabolism. Conclusions: SPP treatment mitigates CCl4-induced hepatic fibrosis in mice. These protective effects may be associated with the modulation of gut microbiota composition and fecal metabolic pathways, including those related to short-chain fatty acid metabolism.