Fructo-oligosaccharides and intestinal barrier function in a methionine–choline-deficient mouse model of nonalcoholic steatohepatitis

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.

Animal models for analyzing metabolic syndrome‐associated liver diseases

“…Based on these findings, we selected male TSOD mice showing hyperglycemia at 6 weeks old for further experiments. The relationship between gut microbiota and NASH is a popular research topic . Similar to other obese mouse models, the abundance of Bacteroidetes was observed to decrease while Firmicutes was observed to increase in TSOD mice .…”

Improvement of Psoriasis by Alteration of the Gut Environment by Oral Administration of Fucoidan from Cladosiphon Okamuranus

“…Dietary fiber is a prebiotic, which is useful in the intestinal environment [11,12]. In the present study, 16S rRNA from intestinal microorganisms in fecal samples was analyzed using next-generation genome sequences.…”

“…Polysaccharides are considered a dietary fiber, and work as prebiotics which are beneficial for the intestinal environment [11]. Fructo-oligosaccharides maintain intestinal barrier function, as does immunoglobulin A (IgA), in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis [12]. Secreted IgA cells in colonic tissue generate mucus that is secreted into the outermost intestinal cecal patch; the secreted mucus entraps bacteria and prevents their translocation into the tissue [13].…”

Gut Microbiota and Nonalcoholic Fatty Liver Disease: Insights on Mechanism and Therapy

“…In methionine-choline-deficient diet-induced steatohepatitis mice model, dietary fructooligosaccharides (FOS) supplementation attenuated the extent of steatohepatitis by restoring the homeostasis of gut microbiota and intestinal epithelial barrier function [120]. Barbara D et al reported that FOS supplement reduced hepatic triglyceride accumulation in n-3 PUFA-depleted diet-induced NAFLD model by altering microbiota composition and increasing production of GLP-1 [121].…”