Discussion
T2DM-associated glucose, T2DM-associated metabolic, T2DM, TG
GCA
In this pilot clinical randomized trial, we demonstrated for the first time that CP, like glipizide, significantly improved HbA1c level and other T2DM-associated glucose metabolism parameters, independent of physical activity and body weight and with no significant effects on liver and kidney function in the patients with T2DM. Moreover, CP also resulted in the improvement in the levels of blood lipid and blood pressure. These results indicate that CP displays a more beneficial effect in the alleviation of T2DM-associated metabolic phenotypes than Glipizide.The improvements in T2DM-associated metabolic phenotypes induced by CP in the study may be explained in part by multiple chemical components in the CP, such as3-caffeoylquinic acid, isoquercitrin and kaempferol-3-glucoside. It has been shown that 3-caffeoylquinic acid is associated with a wide range of biological activities, such as antioxidation, antibacterial, antiparasitic, neuroprotective, anti-inflammatory, anticancer, antiviral, and antidiabetic effect (There is mounting evidence that gut microbiota involves the etiology and progression of T2DM, which has attracted the attention of researchers (On the other hand, our results showed that Glipizide did not significantly affect the composition of intestinal flora during the intervention, which was consistent with the report by Wamg et al (In addition to gut microbiota, metabolites including SCFAs, amino acid catabolites, and BAs produced by gut microbiota play an important role in T2DM development. These metabolites alleviate or exacerbate T2DM via their homologous receptors-mediated signaling (The results of BAs profiling indicated that the regulation of BA signal might be involved in the effect of CP on T2DM patients. On Day 84 of intervention, unconjugated BAs (CDCA, 12-KLCA and β-MCA) levels were increased, while conjugated BAs (GCDCA and TDCA) levels were reduced in the CP group compared with Day 0. Mantovani et al. reported that T2DM was significantly associated with the higher levels of conjugated BAs (TCDCA, TDCA, GCDCA, GDCA and GCA) as well as the lower level of unconjugated BAs (CA) (Collectively, our results indicate that CP increases the levels of SCFAs and unconjugated BAs and decreases the levels of conjugated BAs, thus leading to the improvements in HbA1c and other metabolic indicators.At last, FMT in pseudo-sterile mice was conducted to confirm the causal relationship between the gut microbiota and the effect of CP on host glucose metabolism. The results showed that glucose metabolism parameters (FBG and OGTT glucose AUC) had a significant improvement in the mice transplanted with the post-intervention microbiota from the CP group compared with the mice transplanted with pre-intervention microbiota. Zhang et al. Reported that transplanted fecal bacteria from individuals with normal glucose tolerance altered gut microbiota composition and improved FBG, 2hPBG, TC, TG, and LDL-c in db/db mice (