The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

Abstract

Eucommia ulmoides leaves (EL) are rich in phenolic acids and flavonoids, showing enhancing intestinal health effects. The intestinal microbiota-bile acid axis plays important roles in the occurrence and recovery of inflammatory bowel disease (IBD). However, whether EL extract (ELE) has regulatory effects on the intestinal microbiota, bile acid metabolism, and IBD is still unclear. To fill this gap, 2% dextran sulfate sodium (DSS)-induced mild IBD in a C57BL/6J mouse model that was treated with 200 or 400 mg/kg (intake dose/body weight) ELE was used. Oral ELE supplementation alleviated DSS-induced shortening of colon and colonic epithelial injury. Compared with the DSS group, ELE supplementation significantly decreased Toll-like receptor 4 (TLR4) and interlukin-6 (IL-6) and increased occludin and claudin-1 mRNA expression level in the colon (p < 0.05). Combined 16S rRNA gene sequencing and targeted metabolomic analyses demonstrated that ELE significantly improved the diversity and richness of the intestinal microbiota, decreased the abundance of Bacteroidaceae, and increased Akkermansiaceae and Ruminococcaceae abundance (p < 0.05) compared with DSS-induced IBD mice. Moreover, ELE significantly increased the serum contents of deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA), which were highly positively correlated with Akkermansia and unidentified_Ruminococccaceae relative to the DSS group. We then found that ELE increased Takeda G-protein coupled receptor 5 (TGR5), claudin-1, and occludin mRNA expression levels in the colon. In the Caco-2 cell model, we confirmed that activation of TGR5 improved the reduction in transepithelial electoral resistance (TEER) and decreased the permeability of FITC-dextran on monolayer cells induced by LPS (p < 0.05). siRNA interference assays showed that the decrease in TGR5 expression led to the decrease in TEER, an increase in FITC-dextran permeability, and a decrease in claudin-1 protein expression in Caco-2 cells. In summary, ELE alleviated IBD by influencing the intestinal microbiota structure and composition of bile acids, which in turn activated the colonic TGR5 gene expression in the colon and promoted the expression of tight junction proteins. These findings provide new insight for using ELE as a functional food with adjuvant therapeutic effects in IBD.

Tang-Ping-San Decoction Remodel Intestinal Flora and Barrier to Ameliorate Type 2 Diabetes Mellitus in Rodent Model

“… 37 Eucommia ulmoides balanced the structure and composition of intestinal microflora and improved intestinal tissue morphology. 38 Berberine directly inhibited the growth of Escherichia coli in the intestinal tract, changed the structure of the GM, and controlled blood glucose levels. 39 …”

“…37 Eucommia ulmoides balanced the structure and composition of intestinal microflora and improved intestinal tissue morphology. 38 Berberine directly inhibited the growth of Escherichia coli in the intestinal tract, changed the structure of the GM, and controlled blood glucose levels. 39 We performed 16S rRNA high-throughput sequencing to compare the composition of the GM between the control, model, and TPS-H groups to explore the association between GM and T2DM.…”

Research progress on the relationship between intestinal microecology and intestinal bowel disease

“…In particular, ACE by mediating the intestinal SDF‐1/CXCR4 signaling pathway through the microbiota‐metabolic network it can futher repair the integrity of the intestinal barrier and by reduce the expression of Cyclin D1 and C‐myc, increasing the level of propionic acid and butyric acid. 149 Extract leaves (EL), 150 Bilobalide (BI), 151 Rhodiola crenulata extract (RCE), 152 ginger extract, 153 ethanol extract of Ganoderma lucidum (GL95), 154 flavonoid extracts of Smilax glabra Roxb one of the functions of these extracts is to significantly increase the diversity and richness of the gut microbiota and reverse gut dysbiosis. 155 Gallic acid can regulate the ratio of Firmicutes and Proteobacteria in the gut microbiota of DSS‐UC mice to induce metabolic changes; the main focus is on increasing carbohydrate metabolism (glucose‐related metabolism) and bile acid (BA) metabolism and reducing amino acid metabolism, thereby restoring intestinal microbial homeostasis.…”

Nicotinamide mononucleotide supplementation protects the intestinal function in aging mice and d-galactose induced senescent cells

“…Western blotting was conducted following a previously described method. 24 The protein supernatant was mixed with loading buffer and denatured at 95 °C for 5 min. In electrophoresis, 10 µg protein samples were loaded and separated by running SDS-PAGE gels, and then the gels were transferred to a nitrocellulose membrane.…”