Prebiotic Xylo-Oligosaccharides Ameliorate High-Fat-Diet-Induced Hepatic Steatosis in Rats.

Sanna Lensu,Satu Pekkala,Maarit Lehti,Raghunath Pariyani,Jere Lindén,Leo Lahti,Eveliina Munukka,Marja Tiirola,Anastasiia Driuchina,Elina Mäkinen,Wisam Saleem,Baoru Yang

doi:10.3390/nu12113225

Abstract

Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic β-oxidation and mitochondrial respiration. Nuclear magnetic resonance (1H-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.

Highlights

In western countries, around 30% of the normal weight and up to 90% of the obese population are estimated to suffer from non-alcoholic fatty liver disease (NAFLD) [1]
After 12 weeks of dietary XOS supplementation, F. prausnitzii abundance was increased compared to the high-fat diet (HFD) (Cohen’s d = 0.2) and low-fat diet (LFD) (Cohen’s d = 0.2) without
We show that the prebiotic diet had only minor whose low relative abundance we have previously found to be associated with high hepatic fat content effects on the gut microbiota (GM) in general

Summary

Introduction

Around 30% of the normal weight and up to 90% of the obese population are estimated to suffer from non-alcoholic fatty liver disease (NAFLD) [1]. NAFLD is defined as excessive fat accumulation in the liver without the patient drinking excessive alcohol or using steatogenic drugs. NAFLD can be categorized into simple hepatic steatosis, which is diagnosed as the presence of fat Nutrients 2020, 12, 3225; doi:10.3390/nu12113225 www.mdpi.com/journal/nutrients. Nutrients 2020, 12, 3225 accumulation without histological or biochemical injuries, and non-alcoholic steatohepatitis (NASH), which is characterized by hepatic steatosis, inflammation and damage of the hepatocytes [2,3]. Increasing evidence shows that the pathogenesis of NAFLD is associated with environmental, host genetic and physiological factors [4], such as increased lipid storage [5,6,7] and mitochondrial dysfunction [7]. The GM refers to the trillions of tiny microbial cells inhabiting the gastrointestinal tract that break down the macromolecules and nutrients from the ingested food

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Conclusion