Tisochrysis lutea influences the gut microbiota and cholesterol levels in high-fat diet rats

Modulating the gut microbiota is increasingly recognized as a promising strategy to improve cardiometabolic health, and microalgae are emerging as potential dietary interventions. This study investigated the impact of dietary supplementation with the marine microalga Tisochrysis lutea F&M-M36 on gut microbiota composition and various cardiometabolic parameters in rats. Animals were fed for three months with either a normal-fat (NF) diet, a high-fat (HF) diet, or an HF diet enriched with 5% T. lutea (HFTiso). Gut microbial communities were profiled through 16S rRNA gene sequencing and correlated with plasma lipid levels, glucose, blood pressure, fecal lipid excretion, and adiponectin concentrations. HFTiso supplementation induced significant changes in metabolic traits and reshaped intestinal microbial communities. Multivariate analyses revealed distinct clustering of metabolic profiles according to treatment, with the HFTiso group positioned between HF and NF. Beta-diversity analyses confirmed pronounced treatment-specific shifts, while alpha-diversity remained unchanged. LDA identified 35 discriminative genera, highlighting an enrichment in the HFTiso group of SCFA-producing and lipid-metabolizing. In contrast, HF diets were associated with Clostridium sensu stricto 1 and Terrisporobacter. Positive correlations between HFTiso-associated taxa and adiponectin levels suggest microbiota-driven metabolic benefits. A notable finding was the downregulation, induced by T. lutea, of colonic Niemann-Pick C1-like 1 expression, a key transporter involved in cholesterol absorption, potentially mediated by SCFA-related pathways. These combined effects, direct modulation of host lipid transport and indirect microbiota-driven mechanisms, likely underlie the observed improvements in cardiometabolic outcomes. The bioactivity of T. lutea likely stems from its content of PUFAs, oleic acid, phytosterols, and fucoxanthin; however, it remains unclear whether these compounds act synergistically or whether specific components are chiefly responsible, a question with important implications for developing new preventive or therapeutic strategies for cardiometabolic disorders.