Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis.

Takashi Nakanishi,Yutaka Makizaki,Yoshiki Tanaka,Xuan Wang,Haruka Yokota,Tadayuki Oshima,Hiroshi Ohno,Hirokazu Fukui,Shin Nishiumi,Toshihiko Tomita,Hiroto Miwa

doi:10.3390/cells10113168

Abstract

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.

Highlights

Accumulating evidence has revealed that the gut microbiome plays pivotal roles in the pathophysiology of various diseases, such as inflammatory disorders [1], metabolic syndromes or psychological disorders affecting the whole body [2]
No difference in length was evident (Figure 1D), the serum level of fluorescein isothiocyanate (FITC) was significantly higher in the high-fat diet (HFD) group than in the controls (Figure 1E), suggesting that intestinal permeability had accelerated in the HFD-fed mice
We investigated the mRNA expression of tight junction proteins, which play a pivotal role in the barrier function of the small-intestinal mucosa

Summary

Introduction

Accumulating evidence has revealed that the gut microbiome plays pivotal roles in the pathophysiology of various diseases, such as inflammatory disorders [1], metabolic syndromes or psychological disorders affecting the whole body [2]. It has been reported that a high-fat diet (HFD) is a potent inducer of gut microbiota imbalance (dysbiosis) and responsible for the development of metabolic diseases (obesity or diabetes) [7]. It still remains unclear how HFD-related dysbiosis is involved in dysfunction of the intestinal mucosal barrier and/or steatohepatitis. To clarify the role of HFD-related dysbiosis in the intestinal mucosal barrier and/or steatohepatitis, we comprehensively investigated the liver pathology and the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity

Methods

Results

Conclusion