Early-Life Supplementation of Grape Pomace Extracts Lastingly Promotes Polyphenol Metabolism and Optimizes Gut Microbiota

Abstract

Background: Previous investigations have reported that nutritional supplementation in a critical developmental window can strikingly influence health level and metabolic status in adult life. Grape polyphenol harbors many physiological properties, especially in regulating metabolic status. In the present study, we aimed to investigate whether the GPE supplementation in a vital window plays an important role in metabolic and health status in adult life, by promoting the polyphenol metabolism and optimizing host gut microbiota. Methods: One group of 3-week-old mice and one group of 6-week-old mice were given GPE by gavage for 12 days, and the other group of 3-week- or 6-week- old mice were given by normal saline as control. We detected polyphenol metabolites in the plasma by UPLC-MS/MS. We also used Real-time quantitative RT-PCR to examine mRNA expression levels of genes related to polyphenol metabolism. Furthermore, we analysed the structure of gut microbiota and the correlation between the mRNA expression levels of polyphenol metabolism related genes and gut microbiota. Findings: There were a considerably more abundance of polyphenol metabolites in plasma of 3-week-old mice than that in plasma of 6-week-old mice. Consequently, much higher mRNA expression levels of polyphenol metabolism related genes were observed in intestine of 3-week-old mice. Moreover, after GPE supplementation, the gut microbiota of 3-week-old mice was characterized by a drastic expansion of Akkermansia and Lactobacillus, and a remarkable inhibition of norank_f__Lachnospiraceae, unclassified_f__Lachnospiraceae, Mucispirillum, in comparison with that of 6-week-old mice. In addition, Akkermansia and Lactobacillus had the positive connections with the mRNA expression levels of genes related to polyphenol metabolism in jejunum, such as LPH, SGLT1, SULT1A1, UGT1A1, UGT1A4, UGT1A6. Interpretation: GPE supplementation in a critical developmental window promoted polyphenol absorption and modulated gut microbial community structure, which might contribute to metabolic status and the long-term health. Funding Statement: National Key Research and Development Plan during the 13th five-year plan period (No. 2017YFD0400504). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal study was approved by the China Agricultural University Laboratory Animal Welfare and Animal Experimental Ethical Committee (Beijing, China).