Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, ‘an apple a day keeps the doctor away’. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the “gut microbiota-barrier axis”. Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the “gut microbiota-barrier axis” was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.

Phlorizin (PHZ), a type of dihydrochalcone widely found in Rosaceae such as apples, is the first compound discovered as a sodium-glucose cotransporter (SGLT) inhibitor. It has been confirmed to improve the symptoms of diabetes and diabetic complications effectively. Like other flavonoids, the bioavailability challenge of PHZ is the wide phase I and II metabolism in the digestive tract. In this study, we investigated the pharmacokinetics and contribution of phase II metabolism after the oral and intravenous administrations of PHZ in rats having type 2 diabetes (T2D) and in normal rats. The phase II metabolism characteristics of PHZ were investigated by treating plasma samples with β-glucuronidase/sulfatase. The contribution ratio of phase II metabolism of PHZ ranged from 41.9% to 69.0% after intravenous injection with three doses of PHZ in normal rats. Compared with the observations for normal rats, AUC_0−t and C_max of PHZ significantly increased and T_1/2 of PHZ significantly decreased in T2D rats. PHZ was converted into phloretin (PHT) through an enzyme-catalyzed hydrolysis reaction, and PHT was further transformed into conjugates with glycose after both oral and intravenous administrations. Moreover, it was found that the bioavailability of PHZ was about 5% in T2D rats, which was significantly higher than that in normal rats (0%). In conclusion, compared with the observations for normal rats, the pharmacokinetic characteristics of PHZ significantly changed in T2D rats through oral and intravenous administrations. The bioavailability of PHZ significantly increased in T2D rats. Besides, the phase II metabolites of PHT were the major existing forms in blood after oral and intravenous administrations. Our results indicated that the phase II metabolism characteristics of PHZ should be considered when PHZ is applied for the treatment of diabetes as a drug or functional food.

Lilium regale Wilson (L.regale), originated in the Minjiang River basin in Sichuan, China, has different phenotypic characteristics in different environments. To analyze the correlation between the phenotypes of L.regale and its soil micro-ecological environment, wild habitat soil of L.regale at the two altitudes were selected to analyze the diversity and community structure of microorganisms in soil, and measure the soil physicochemical factors and enzyme activities. The structural composition and diversity of fungal and bacterial communities in hillside and valley soils were significantly different (p< 0.01). Soil available potassium (AK) and soil enzyme activities such as urease (S_UE), sucrase (S_SC), and catalase (S_CAT) differed significantly different between hillsides and valleys (p < 0.01), while organic matter (OM), total phosphorus (TP), and polyphenol oxidase (S_PPO) had no great variances. Correlation analysis was conducted between the common and differential microorganisms and the morphological characteristics, soil physicochemical factors and soil enzyme activities of L.regale in both hillside and valley. The results showed that both of the fungal and bacterial could be clustered into two distinct groups by positive and negative correlations, suggesting that the representative microorganism may have structural characteristics that are directly related to soil physicochemical properties and enzyme activities, which conversely affect the phenotype of Lily. Therefore, the study on the native species of horticultural plants and the local soil microhabitat environment will benefit the conservation of wild Lily and provide theoretical guidance for the domestication and breeding of horticultural plants.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

Unhealthy diets rich in fats and/or sugar are considered as the major external cause of the obesity epidemic, which is often accompanied by a significant decrease in gut hormone glucagon-like peptide-1 (GLP1) levels. Numerous studies have demonstrated notable contributions of the gut microbiota in this process. Nevertheless, the underlying mechanism still needs further investigation. The role of epigenetic modifications in gene expression and metabolism has been well demonstrated, with m6A methylation on RNAs being the most prevalent modification throughout their metabolism. In the present study, we found that the expressions of small intestinal Gcg and Pc3, two key genes regulating GLP1 expression, were significantly downregulated in obese mice, associated with reduced GLP1 level. Immunohistochemistry analysis indicated that a high-fat diet slightly increased the density of enteroendocrine L cells in the small intestine, implying that decreased GLP1 levels were not caused by the changes in L cell intensity. Instead, the small intestinal m6A level as well as the expression of known “writers”, mettl3/14 and wtap, were found to be positively correlated with the expression of Gcg and Pc3. Fecal microbiota transplantation with feces from normal and obese mice daily to antibiotic-treated mice revealed that dysbiosis in diet-induced obesity was sufficient to reduce serum GLP1, small intestinal m6A level, and intestinal expressions of Gcg, Pc3, and writer genes (mettl3/14, wtap). However, as the most direct and universal methyl donor, the production of fecal S-adenosylmethionine was neither affected by the different dietary patterns nor their shaped microbiota. These results suggested that microbial modulation of the epitranscriptome may be involved in regulating GLP1 expression, and highlighted epitranscriptomic modifications as an additional level of interaction between diet and individual health.