Abstract
Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine–choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine–choline-deficient diet, a methionine–choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet. Fecal bacteria, short-chain fatty acids, and immunoglobulin A (IgA) levels were investigated. Histological and immunohistochemical examinations were performed using mice livers for CD14 and Toll-like receptor-4 (TLR4) expression and intestinal tissue samples for IgA and zonula occludens-1 expression in epithelial tight junctions. The methionine–choline-deficient mice administered 5% fructo-oligosaccharides maintained a normal gastrointestinal microbiome, whereas methionine–choline-deficient mice without prebiotic supplementation displayed increases in Clostridium cluster XI and subcluster XIVa populations and a reduction in Lactobacillales spp. counts. Methionine–choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine–choline-deficient mice that were not administered this prebiotic. This study illustrated that in the methionine–choline-deficient mouse model, dietary fructo-oligosaccharides can restore normal gastrointestinal microflora and normal intestinal epithelial barrier function, and decrease steatohepatitis. The findings support the role of prebiotics, such as fructo-oligosaccharides, in maintaining a normal gastrointestinal microbiome; they also support the need for further studies on preventing or treating nonalcoholic steatohepatitis using dietary fructo-oligosaccharides.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is an organ phenotype in metabolic syndrome that is often complicated by obesity, dyslipidemia, and diabetes mellitus [1]
In Nonalcoholic steatohepatitis (NASH), dysbiosis has been determined via fecal examination, and it is caused by an unbalanced diet or obesity, suggesting that improvements of the microbial flora are correlated with improvements of hepatic steatosis [6]
Regarding the bacterial balance in feces of methionine–choline-deficient diet (MCD) mice compared with that in control mice’s feces, it was recognized that Clostridium cluster XI levels increased from 3% to 8.7%, and those of the Clostridium subcluster XIVa increased from 5.9% to 26.3%; on the contrary, counts of Lactobacillales spp. decreased from 45.9% to 5.1% (Fig 1)
Summary
Nonalcoholic fatty liver disease (NAFLD) is an organ phenotype in metabolic syndrome that is often complicated by obesity, dyslipidemia, and diabetes mellitus [1]. Nonalcoholic steatohepatitis (NASH) is part of the spectrum of NAFLD, combined with hepatic inflammation and fibrosis, leading to cirrhosis [2]. According to an analysis of the microbial flora and a study of metabolic products, intestinal bacteria participate in organic homeostasis and pathological changes in the living body [4]. Abnormality of the microbial flora is called dysbiosis, which denotes a lack of diversity of intestinal bacteria because of a disorder of quantitative and qualitative balance [5]. In NASH, dysbiosis has been determined via fecal examination, and it is caused by an unbalanced diet or obesity, suggesting that improvements of the microbial flora are correlated with improvements of hepatic steatosis [6]
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