Integrated microbiome and untargeted metabolomics analyses reveal the mechanism by which Haematococcus pluvialis polysaccharide alleviates obesity.

Haematococcus pluvialis is a microalga with substantial nutritional and medicinal value. This study aimed to investigate the anti-obesity efficacy of Haematococcus pluvialis polysaccharide (HP) in high-fat diet (HFD)-induced obese mice. Structural characterization revealed that HP was mainly composed of glucose, rhamnose, arabinose, galactose, fructose, xylose, galacturonic acid, and glucuronic acid, with molar ratios of 74.14%, 0.87%, 2.98%, 3.19%, 0.88%, 17.05%, 0.05%, and 0.90%, respectively. Its molecular weight was 1.363 × 104 Da. Results from animal experiments showed that HP significantly suppressed body weight gain in HFD-fed obese mice and exerted beneficial anti-obesity effects. Furthermore, HP effectively alleviated HFD-induced abnormalities in glycolipid metabolism, systemic inflammation, and fat fat accumulation in the liver and epididymal adipose tissue. High-throughput fecal 16S rRNA gene sequencing revealed that HP corrected HFD-induced gut microbial dysbiosis, significantly modulating the structure and diversity of the gut microbiota in mice. HP notably increased the relative abundance of beneficial genera, including Bacteroides, Allobaculum, Dorea, and Butyricicoccus. Untargeted metabolomic analysis further demonstrated that HP markedly upregulated the relative levels of gut microbiota-associated metabolites such as indole and sulfated cholic acid. These changes directly affected metabolic pathways closely linked to glycolipid homeostasis, including bile acid metabolism and tryptophan metabolism. Therefore, Haematococcus pluvialis polysaccharide could serve as a promising anti-obesity bioactive compound for intervening metabolic disorders in obese individuals.