Liupao tea, a popular dark tea, exhibited anti-diabetic activity in Chinese tea culture. However, the bioavailability of the main active components is low. Therefore, the relationship between the anti-diabetic activity and the modulation of gut microbiota was investigated in this study for the first time. Liupao tea extract (LTE) could significantly alleviate hyperglycemia, insulin-resistance, and plasma lipid profiles. The hypoglycemic effect of high-dose LTE was comparable to that of metformin. Importantly, LTE exhibited beneficial effect on modulating the diabetic-induced disorder of gut microbiota, such as increasing Bacteroidetes/Firmicutes ratio and up-regulating putative short-chain fatty acid (SCFA)-producing bacteria, including Prevotella and Bacteroides. Moreover, 29 key phylotypes were significantly correlated with at least one diabetic index. In conclusion, LTE could be developed into an anti-diabetic functional beverage and its beneficial effects is likely to be associated with the prebiotic effects for increasing the level of SCFAs and the relative abundance of SCFA-producing bacteria.

Background: The co-culture strategy which mimics natural ecology by constructing an artificial microbial community is a useful tool to activate the biosynthetic gene clusters to generate new metabolites. However, the conventional method to study the co-culture is to isolate and purify compounds separated by HPLC, which is inefficient and time-consuming. Furthermore, the overall changes in the metabolite profile cannot be well characterized. Results: A new approach which integrates computational programs, MS-DIAL, MS-FINDER and web-based tools including GNPS and MetaboAnalyst, was developed to analyze and identify the metabolites of the co-culture of Aspergillus sydowii and Bacillus subtilis. A total of 25 newly biosynthesized metabolites were detected only in co-culture. The structures of the newly synthesized metabolites were elucidated, four of which were identified as novel compounds by the new approach. The accuracy of the new approach was confirmed by purification and NMR data analysis of 7 newly biosynthesized metabolites. The bioassay of newly synthesized metabolites showed that four of the compounds exhibited different degrees of PTP1b inhibitory activity, and compound N2 had the strongest inhibition activity with an IC₅₀ value of 7.967 μM. Conclusions: Co-culture led to global changes of the metabolite profile and is an effective way to induce the biosynthesis of novel natural products. The new approach in this study is one of the effective and relatively accurate methods to characterize the changes of metabolite profiles and to identify novel compounds in co-culture systems.