Multi-omics reveals gut microbiome- and metabolome-specific responses to sugar alcohols

The impacts of sugar alcohols (SA) utilized as low-calorie sweeteners on the gut microbiome and metabolome remain undefined. Among six SAs tested, isomalt, erythritol, xylitol and sorbitol significantly lowered fasting serum insulin and hepatic lipid levels in healthy rats, while mannitol and maltitol showed no such effect. Moreover, isomalt consumption lowered body weight gain, low-density lipoprotein and tumor necrosis factor-α, while improving high-density lipoprotein concentrations. All SAs effectively regulated gut microbiota composition and functionality. Most of the microbiota enriched by isomalt were short-chain fatty acid producers, including Faecalibaculum, Bacillus, Dubosiella and Anaerostipes, which led to a significant increase in the propionate proportion in faeces. The elevated Blautia and UCG-008 and lowered Akkermansia were the key specific responders to sorbitol, mannitol and maltitol. Notably, almost all SAs showed inhibitive efficacy on opportunistic pathogens such as Streptococcus, Staphylococcus and Ruminococcus. Dietary SAs significantly shifted stool and global metabolome profiles in rats. Isomalt and maltitol activated aldosterone-regulated sodium reabsorption and suppressed steroid hormone biosynthesis. Isomalt and sorbitol induced the thyroid hormone signaling pathway. Erythritol intake expressively triggered histamine metabolism, chemical carcinogenesis-receptor activation and folate biosynthesis. Xylitol, sorbitol and mannitol robustly promoted nucleotide metabolism, lysine biosynthesis and pyrimidine metabolism. Sorbitol and mannitol administration induced arginine biosynthesis, nicotinate and nicotinamide metabolism and terpenoid backbone biosynthesis. Additionally, stool metabolome suggested that mannitol intake attenuated ferroptosis in rats. Interestingly, structurally similar SAs, e.g. sorbitol, mannitol and maltitol, showed more shared microbiota and metabolites. This systematic comparative study identifies specific microbiota and associated metabolic pathways as responders to each SA and provides novel insights for future application in functional foods.