Nannochloropsis polysaccharides ameliorate alcohol-associated liver injury by modulating the cGAS-STING-NF-κB signaling pathway

Gut microbial composition and diet-induced alterations in the gut microbiota are closely linked to the progression and severity of alcoholic liver disease (ALD). Our prior research identified that Nannochloropsis polysaccharides (NPS) are enriched in ribose and possess gut microbiota-reshaping properties. In the present study, we demonstrated that NPS decreased the relative abundance of Gram-negative bacteria and alleviated alcohol-induced liver injury in mice. Moreover, NPS reduced bacterial endotoxin lipopolysaccharide (LPS) levels and concurrently upregulated the expression of intestinal tight junction proteins. Mechanistically, fecal microbiota transplantation (FMT) experiments confirmed that the NPS-reshaped gut microbiota mitigated hepatic LPS accumulation, thereby alleviating mitochondrial damage, reducing mitochondrial DNA release, and further suppressing activation of the cGAS-STING-NF-κB signaling pathway, ultimately contributing to the attenuation of ALD. Collectively, these findings demonstrate that NPS mainly alleviates ALD through modulation of the gut microbiota, thus providing a promising strategy for the high-value utilization of Nannochloropsis processing by-products. • NPS reduced the levels of transaminases and inflammatory factors in ALD mice. • NPS reshaped the composition of the gut microbiota and reduced LPS level. • NPS alleviated ALD by inhibiting the activation of the cGAS-STING-NF-κB pathway.