Threitol, a Novel Functional Sugar Alcohol Biosynthesized by Engineered Yarrowia lipolytica, Has the Potential as a Low-Calorie Sugar-Reducing Sweetener

The global obesity and metabolic syndrome epidemic have accelerated demand for reduced-sugar food, prompting the food industry to adopt functional sugar alcohols as sucrose substitutes. Threitol is a four-carbon sugar alcohol and an isomer of erythritol. However, there is a scarcity of studies reporting on the edible safety of threitol. This study assessed threitol's toxicological and metabolic properties. Acute oral administration (10 g/kg) caused no mortality or abnormalities in mice. Repeated 28-day exposure revealed no behavioral or histopathological alterations, with negative outcomes in three genotoxicity tests. Metabolic studies in rats demonstrated that the majority of ingested threitol is excreted in the urine within 24 h. Sensory evaluation indicated threitol's sweetness equivalence to sucrose, exceeding erythritol and allulose. Notably, 16S rRNA sequencing revealed gut microbiota modulation in threitol-fed mice, indicating potential intestinal health benefits. These integrated findings establish threitol's preclinical safety and support its development as a novel low-calorie sweetener.