An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High‐Fat Diet‐Fed Mice

Abstract

ScopeTo analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high‐fat (HF) diet.Methods and resultsThree‐month‐old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX‐5 mg kg−1) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr‐Fgf15, Tgr5‐Glp1, and Cldn‐Ocldn‐Zo1 is increased, and Tlr4‐Il6‐Il1beta is decreased.ConclusionFEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.

Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea

“…RNA was reverse-transcribed into complementary DNA (cDNA) using a commercial kit (Thermo Fisher Scientific, Waltham, MA, USA) and a T100 (Bio-Rad, Hercules, CA, USA) thermocycler. The mRNA levels in the colon were detected by GoScript Reverse Transcription System (Promega Biotech, Beijing, China) on a CFX 96 real-time system instrument (Bio-Rad, Hercules, CA, USA) with the following amplification program: 95 °C 120 s and 45 cycles of 95 °C for 5 s, 64 °C for 30 s and 72 °C for 30 s using specific primers ( Table S2 ) [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The housekeeping gene beta-actin was used to standardize the gene expression, and the relative expression level of each gene was calculated using the 2 −ΔΔCT method [ 31 ].…”