The “gut–liver” axis plays an important role in the mechanism of alcoholic liver disease (ALD). Sporidiobolus pararoseus polysaccharides (SPP) have been shown to improve the gut barrier and liver damage in mice with ALD. However, the process is modulated via the gut microbiome and amino acids in the gut–liver axis has not been elucidated. In this study, the gut microbiome and metabolic function were explored for the mechanism by which SPP improve ALD. The results showed that after the SPP were metabolized by ALD mice, microbial diversity was altered, and the relative abundances of Lachnospiraceae, Alistipes, Eubacterium siraeum, and Bacteroides increased. The predicted results of microbiome functions promoted the biosynthesis of amino acids, tyrosine, tryptophan, valine, leucine, and isoleucine were enhanced. Metabolomics results also confirmed that butanoate metabolism and biosynthesis of phenylalanine, tyrosine, and tryptophan are the main regulatory pathways of SPP. The gut microbiome metabolizes the hallmark metabolites of SPP were l-tyrosine, l-histidine, and l-serine. Correlation analysis and interaction network deeply mine gut microbiome (Lachnospiraceae, Eubacterium siraeum, Erysipelotrichaceae), metabolites (L−serine, L−tyrosine), and metabolism (biosynthesis of amino acids, valine, leucine, and isoleucine biosynthesis) may be key factors in the SPP-gut microbiome–metabolites–metabolism in ALD mice. Therefore, SPP have the effect of proliferating beneficial gut microbiome that metabolize polysaccharides, promoting the production of amino acids, and regulating liver metabolic disorders.
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