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. 2018 Dec 5;23(12):3213.
doi: 10.3390/molecules23123213.

Modulation of Gut Microbiota by Lonicera caerulea L. Berry Polyphenols in a Mouse Model of Fatty Liver Induced by High Fat Diet

Shusong Wu  1   2 , Ruizhi Hu  3 , Hironobu Nakano  4 , Keyu Chen  5 , Ming Liu  6 , Xi He  7 , Hongfu Zhang  8 , Jianhua He  9 , De-Xing Hou  10   11
Affiliations

Modulation of Gut Microbiota by Lonicera caerulea L. Berry Polyphenols in a Mouse Model of Fatty Liver Induced by High Fat Diet

Shusong Wu et al. Molecules. .

Abstract

Polyphenols from the Lonicera caerulea L. berry have shown protective effects on experimental non-alcoholic fatty liver disease (NAFLD) in our previous studies. As endotoxins from gut bacteria are considered to be the major trigger of inflammation in NAFLD, this study aims to clarify the regulatory effects of L. caerulea L. berry polyphenols (LCBP) on gut microbiota in a high fat diet (HFD)-induced mouse model. C57BL/6N mice were fed with a normal diet, HFD, or HFD containing 0.5⁻1% of LCBP for 45 days. The results revealed that supplementation with LCBP decreased significantly the levels of IL-2, IL-6, MCP-1, and TNF-α in serum, as well as endotoxin levels in both serum and liver in HFD-fed mice. Fecal microbiota characterization by high throughput 16S rRNA gene sequencing revealed that a HFD increased the Firmicutes/Bacteroidetes ratio, and LCBP reduced this ratio by increasing the relative abundance of Bacteroides, Parabacteroides, and another two undefined bacterial genera belonging to the order of Bacteroidales and family of Rikenellaceae, and also by decreasing the relative abundance of six bacterial genera belonging to the phylum Firmicutes, including Staphylococcus, Lactobacillus, Ruminococcus, and Oscillospira. These data demonstrated that LCBP potentially attenuated inflammation in NAFLD through modulation of gut microbiota, especially the ratio of Firmicutes to Bacteroidetes.

Keywords: Lonicera caerulea L.; fatty liver disease; gut microbiota; inflammation; polyphenols.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The effect of LCBP on serum levels of cytokine. IL-2 (A), IL-6 (B), MCP-1 (C), and TNF-α (D) were measured by using a Bio-Plex Pro Mouse Cytokine 23-Plex Panel kit (Bio-Rad Laboratories, Inc., Hercules, CA, USA). The data represent mean ± SD of four mice. Bars with different letters differ significantly (p < 0.05). HFD, High fat diet; LCBP, Lonicera caerulea L. berry polyphenols; IL, interleukin; MCP-1, monocytes chemotactic protein-1; TNF-α, tumor necrosis factor-alpha.
Figure 2
Figure 2
The effect of LCBP on endotoxin levels in serum and liver. The level of endotoxin in mouse serum (A) and liver (B) was measured by using a Pierce LAL Chromogenic Endotoxin Quantitation Kit (Thermo Fisher Scientific Inc., Rockford, IL, USA). The data represents the mean ± SD of four mice. Bars with different letters differ significantly (p < 0.05). HFD, high fat diet; LCBP, Lonicera caerulea L. berry polyphenols.
Figure 3
Figure 3
Modulation of gut microbiota by LCBP at the phylum level. Fecal microbiota were characterized by 16S rRNA gene sequencing. (A) The relative abundance of bacteria including Verrucomicrobia, Proteobacteria, Firmicutes, Deferribacteres, Bacteroidetes and Actinobacteria, at the phylum level. (B) The ratio of Firmicutes to Bacteroidetes, based on their relative abundance. HFD, high fat diet; LCBP, Lonicera caerulea L. berry polyphenols.
Figure 4
Figure 4
The effect of LCBP on the bacterial genera belonging to Bacteroidetes. Fecal microbiota were characterized by 16S rRNA gene sequencing, and the data represents the relative abundance of each bacterial genus. p_, c_, o_, f_, or g_ represents phylum, class, order, family, and genus, respectively, and a blank after the letter means undefined. HFD, high fat diet; LCBP, Lonicera caerulea L. berry polyphenols.
Figure 5
Figure 5
The effect of LCBP on the relative abundance of bacterial genera belonging to Firmicutes. Fecal microbiota were characterized by 16S rRNA gene sequencing, and the data represents the relative abundance of each bacterial genus. p_, c_, o_, f_or g_ represents phylum, class, order, family, and genus, respectively, and a blank after the letter means undefined. HFD, High fat diet; LCBP, Lonicera caerulea L. berry polyphenols.
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