Abstract
Regulation of gut microbiota and modulation of bile acid (BA) composition are potential strategies for the treatment of intestinal inflammation. This study aimed to investigate the effect of grape seed proanthocyanidin (GSP) on intestinal inflammation and to understand its mechanism. C57BL/6J male mice (7–8 weeks old) were used in experiments. Antibiotics were applied to deplete gut microbiota to evaluate the contribution of gut microbiota to the effect of dietary GSP. Intestinal-specific farnesoid X receptor (FXR) inhibitor was used to analyze the role of FXR signaling. In this study, GSP alleviated intestinal inflammation induced by LPS and altered the gut microbiota accompanied by increased abundance of hydroxysteroid dehydrogenase (HSD) producing microbes. GSP activated the intestinal FXR signaling pathway and increased gene expression of enzymes of the alternative BA synthetic pathway, which associated with elevated levels of chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) in liver and feces. However, gut microbiota depletion by antibiotics removed those effects of GSP on mice injected with LPS. In addition, the protective effect of GSP on mice challenged with LPS was weakened by the inhibition of intestinal FXR signaling. Further, the mixture of CDCA and LCA mirrored the effects of GSP in mice injected with LPS, which might verify the efficiency of CDCA and LCA on intestinal inflammation. Taken together, our results indicated that GSP exerted an intestinal protection role in the inflammation induced by LPS, and these effects were mediated by regulating gut microbiota-BA crosstalk.
Highlights
A large number of microorganisms in the intestine formed a symbiotic relationship with the host during long-term evolution
For mRNA expression levels for the hepatic bile acid (BA) synthetic genes, CYP7A1 was not significantly affected (p > 0.05) but CYP8B1 was decreased (p ≤ 0.05), and CYP27A1 and CYP7B1 were increased (p ≤ 0.05) in the grape seed proanthocyanidin (GSP)+LPS group compared to the LPS group. These results indicated that dietary GSP elevated ileal farnesoid X receptor (FXR) signaling activation and increased mRNA for genes in the alternative BA synthetic pathway involving CYP7B1 and CYP27A1, which may lead to the increased production of chenodeoxycholic acid (CDCA) rather than cholic acid (CA)
The concentrations of CDCA and lithocholic acid (LCA) in the feces were lower (p ≤ 0.05) in the LPS and the Gly + GSP + LPS groups than in the GSP + LPS group (Table 4). These results indicated that the beneficial effects of dietary GSP on intestinal inflammation may partly be dependent on the intestinal FXR signaling activation
Summary
A large number of microorganisms in the intestine formed a symbiotic relationship with the host during long-term evolution. Under normal circumstances, these microorganisms do not harm the health of the body, which depends on the body’s complete intestinal mucosal barrier function preventing intestinal harmful microbiota and various types of toxins [1, 2]. Emerging evidence indicates a strong association between the gut microbiota and bile acid (BA) metabolism [4]. Unreabsorbed BAs are converted into secondary BAs by a series of deconjugation and dehydroxylation processes under the action of the gut microbiota-derived enzymes [6]. Changes in the composition of gut microbiota have an important impact on the metabolism of BAs
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