Different time-restricted feeding patterns potentially modulate metabolic health by altering tryptophan metabolism of gut microbes in pigs

Time-restricted feeding has emerged as a preferred approach for alleviating metabolic disorders, but the potential microbiological mechanism remains poorly understood. This study used a growing pig model to mimic common-sense eating habits. Four feeding patterns were set up, including ad libitum feeding (ALF) for daily irregulated eating habits, time-restricted feeding (TRF) for three meals a day, early time-restricted feeding (eTRF) for skipping dinner and mid-day time-restricted feeding (mTRF) for skipping breakfast. The results showed that the three time-restricted feeding patterns (TRF, eTRF and mTRF) resulted in a reduction of hepatic fat accumulation and a decrease in hepatic function markers compared to the ALF pattern. However, this was independent of food consumption. Transcriptome analysis of the liver showed that the three time-restricted feeding patterns downregulated the expression of genes related to gluconeogenesis, β-oxidation, lipid accumulation, and urea cycle, and upregulated the expression of genes related to lipogenesis and glycolysis compared to the ALF pattern. Microbiome and metabolome analyses showed that Lactobacillus enriched in the colon of pigs in three time-restricted groups were negatively correlated with serum triglyceride. Meanwhile, three time-restricted feeding patterns elevated the levels of the microbial metabolite indole-3-lactic acid, which was further confirmed to reduce excessive hepatic lipid accumulation in vitro. Overall, time-restricted feeding potentially improved metabolic health by modulating gut microbiota and metabolites.