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.

Highlights

  • Phytochemicals present in functional foods, such as cool climate berries, offer a great hope as an alternative therapy for chronic disorders [1]

  • Molecules 2018, 23, 3213 studies have suggested that endotoxins or alcohols produced by gut microbiota potentially promote the progression of non-alcoholic fatty liver disease (NAFLD) [7,8], and polyphenols may exert biological functions through interaction with gut microbiota [9]

  • Our previous study showed that LCBP improved hepatic steatosis and insulin resistance [6], which is supposed to be mediated by cytokines [14]

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Summary

Introduction

Phytochemicals present in functional foods, such as cool climate berries, offer a great hope as an alternative therapy for chronic disorders [1]. The berry of L. caerulea L. is rich in polyphenols, anthocyanins (mainly cyanidin 3-glucoside (C3G) [3]), and possesses multiple biological functions [4]. L. caerulea L. berry polyphenols (LCBP) have been shown to be able to protect mice against high fat diet-induced non-alcoholic fatty liver disease (NAFLD), by enhancing the antioxidant capability and inhibiting the production of inflammatory cytokines of mice [5,6]. Molecules 2018, 23, 3213 studies have suggested that endotoxins or alcohols produced by gut microbiota potentially promote the progression of NAFLD [7,8], and polyphenols may exert biological functions through interaction with gut microbiota [9]. We hypothesized that polyphenols from Lonicera caerulea L. berries attenuate

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