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, 2019, 5236149
eCollection

Blueberry Attenuates Liver Fibrosis, Protects Intestinal Epithelial Barrier, and Maintains Gut Microbiota Homeostasis

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Blueberry Attenuates Liver Fibrosis, Protects Intestinal Epithelial Barrier, and Maintains Gut Microbiota Homeostasis

Zhiqiang Yan et al. Can J Gastroenterol Hepatol.

Abstract

Objective: Recently, blueberry has been identified as a candidate for the treatment of liver fibrosis. Given the role of gut-liver axis in liver fibrosis and the importance of the gut microbiota homeostasis to the maintenance of the intestinal epithelial barrier, this study aimed to investigate whether blueberry could attenuate liver fibrosis and protect the intestinal epithelial barrier by maintaining the homeostasis of the gut microbiota.

Method: A CCl4-induced rat liver fibrosis model was used to detect the roles of blueberry in liver fibrosis and intestinal epithelial barrier. The liver weight and body weight were measured, the liver function was monitored by ALT and AST activity, protein and mRNA were determined by western blot and RT-qPCR, and the gut microbiome was detected by Miseq.

Results: The results showed that blueberry could reduce the rate of liver weight/body weight gain (p < 0.05), ALT (p < 0.01) and AST (p < 0.05) activity, and the expression of collagen I (p < 0.01), collagen IV (p < 0.01), and α-SMA (p < 0.01) expression in CCl4-induced rat liver. CCl4 impaired the intestinal epithelial barrier and decreased the expression of the tight junction protein. Blueberry restored the intestinal epithelial barrier and increased the expression of the tight junction protein. The gut microbiota homeostasis was impaired by CCl4, but after treatment with blueberry, the intestinal flora returned to normal.

Conclusion: Blueberry attenuated liver fibrosis, protected intestinal epithelial barrier, and maintained the homeostasis of the gut microbiota in a CCl4-induced injury rat model.

Conflict of interest statement

All authors declare no potential conflicts of interest about this article.

Figures

Figure 1
Figure 1
Blueberry attenuated CCl4-induced liver injury The body weights (a) and liver weights/body weights (b) in the Ctrl, BB, CCl4, and CCl4 + BB groups. The plasma levels of ALT (c) and AST (d) in the Ctrl, BB, CCl4, and CCl4 + BB groups. n = 6. p < 0.05 and ∗∗p < 0.01.
Figure 2
Figure 2
Blueberry attenuated CCl4-induced liver fibrosis. H&E (a) and Masson's (b) staining in rat livers among the Ctrl, BB, CCl4, and CCl4 + BB groups. (c–f) The protein levels of collagen I, collagen IV, and α-SMA in rat livers among the Ctrl, BB, CCl4, and CCl4 + BB groups. Western blot was performed to identify the protein levels. (c) The bands of collagen I, collagen IV, and α-SMA. (d–f) Quantitative analysis of collagen I (d), collagen IV (e), and α-SMA (f). β-Actin acted as a loading control (n = 6, ∗∗p < 0.01).
Figure 3
Figure 3
Blueberry protected intestinal epithelial barrier breakdown induced by CCl4. (a) H&E staining in rat colon among the Ctrl, BB, CCl4, and CCl4 + BB groups. The protein bands (b) and quantitative value (c) of claudin1, claudin2, and ZO1 in rat colon among the Ctrl, BB, CCl4, and CCl4 + BB groups. β-Actin acted as a loading control. (d) The mRNA levels of claudin1, claudin2, and ZO1 in rat colon among the Ctrl, BB, CCl4, and CCl4 + BB groups. GAPDH acted as a loading control (n = 6, p < 0.05 and ∗∗∗∗p < 0.0001).
Figure 4
Figure 4
The heatmap (a), relative abundance (b), and PCA (c) of gut microbiota at the phylum level in the Ctrl, BB, CCl4, and CCl4 + BB groups.
Figure 5
Figure 5
Differences in microbiota composition among the Ctrl, BB, CCl4, and CCl4 + BB groups with linear discriminant analysis effect size (LEFSE), visualized by cladogram (a) and histogram (b).

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References

    1. Friedman S. L. Liver fibrosis—from bench to bedside. Journal of Hepatology. 2003;38:38–53. doi: 10.1016/s0168-8278(02)00429-4. - DOI - PubMed
    1. Yan J., Tung H.-C., Li S., et al. Aryl hydrocarbon receptor signaling prevents activation of hepatic stellate cells and liver fibrogenesis in mice. Gastroenterology. 2019;157(3):793.e14–806.e14. doi: 10.1053/j.gastro.2019.05.066. - DOI - PMC - PubMed
    1. Ye J.-F., Zhu H., Zhou Z.-F., et al. Protective mechanism of andrographolide against carbon tetrachloride-induced acute liver injury in mice. Biological & Pharmaceutical Bulletin. 2011;34(11):1666–1670. doi: 10.1248/bpb.34.1666. - DOI - PubMed
    1. Lee C.-H., Park S.-W., Kim Y. S., et al. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biological & Pharmaceutical Bulletin. 2007;30(10):1898–1904. doi: 10.1248/bpb.30.1898. - DOI - PubMed
    1. Weber L. W. D., Boll M., Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Critical Reviews in Toxicology. 2003;33(2):105–136. doi: 10.1080/713611034. - DOI - PubMed

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