Isoquercetin and inulin synergistically modulate the gut microbiome to prevent development of the metabolic syndrome in mice fed a high fat diet

Si Tan,Henrietta Koch,Vance B Matthews,Kevin D Croft,Natalie C Ward,Fergal O’Gara,Jose A Caparros-Martin

doi:10.1038/s41598-018-28521-8

Abstract

Dietary fibre positively influences gut microbiome composition, enhancing the metabolism of dietary flavonoids to produce bioactive metabolites. These synergistic activities facilitate the beneficial effects of dietary flavonoids on cardiometabolic health parameters. The aims of this study were to investigate whether isoquercetin (a major dietary flavonoid) and inulin (soluble fibre), either alone or in combination could improve features of the metabolic syndrome. Following a 1 week acclimatization, male C57BL6 mice (6–8 weeks) were randomly assigned to; (i) normal chow diet (n = 10), (ii) high fat (HF) diet (n = 10), (iii) HF diet + 0.05% isoquercetin (n = 10), (iv) HF diet + 5% inulin, or (v) HF diet + 0.05% isoquercetin + 5% inulin (n = 10). Body weight and food intake were measured weekly. At 12 weeks, glucose and insulin tolerance tests were performed, and blood, faecal samples, liver, skeletal muscle and adipose tissue were collected. At 12 weeks, mice on the HF diet had significantly elevated body weights as well as impaired glucose tolerance and insulin sensitivity compared to the normal chow mice. Supplementation with either isoquercetin or inulin had no effect, however mice receiving the combination had attenuated weight gain, improved glucose tolerance and insulin sensitivity, reduced hepatic lipid accumulation, adipocyte hypertrophy, circulating leptin and adipose FGF21 levels, compared to mice receiving the HF diet. Additionally, mice on the combination diet had improvements in the composition and functionality of their gut microbiome as well as production of short chain fatty acids. In conclusion, long-term supplementation with the dietary flavonoid isoquercetin and the soluble fibre inulin can attenuate development of the metabolic syndrome in mice fed a high fat diet. This protective effect appears to be mediated, in part, through beneficial changes to the microbiome.

Highlights

The metabolic syndrome is defined as a series of risk factors that commonly cluster together, increasing the risk of both cardiovascular disease (CVD) and type 2 diabetes (T2DM)[1,2]
Isoquercetin (ISO), a glucoside of quercetin that is commercially available in pure form, and inulin (INU), a non-digestible polysaccharide, were used as sources of flavonoid and fibre, which were added to a high fat (HF) diet and fed to male C57BL6 mice for a period of 12 weeks
Supplementation of the HF diet with either isoquercetin or inulin alone had no effect on weight gain

Summary

Introduction

The metabolic syndrome is defined as a series of risk factors that commonly cluster together, increasing the risk of both cardiovascular disease (CVD) and type 2 diabetes (T2DM)[1,2]. Inulin is a soluble dietary fibre composed of a group of naturally occurring polysaccharides, which are not digested in the intestine but instead, fermented into short-chain fatty acids (SCFAs) These SCFAs have been associated with several key metabolic processes, including adiposity, food intake, lipid metabolism, glucose homeostasis and insulin resistance[14,15]. In addition to these prebiotic characteristics, inulin plays a role in regulating hepatic lipid metabolism and improving lipid profiles[16,17]. The aims of this study were to investigate the long-term effects of flavonoid and fibre supplementation, alone and in combination, on gut microbiome composition and development of the metabolic syndrome in mice fed a high fat diet. Isoquercetin (ISO), a glucoside of quercetin (a common dietary flavonoid) that is commercially available in pure form, and inulin (INU), a non-digestible polysaccharide, were used as sources of flavonoid and fibre, which were added to a high fat (HF) diet and fed to male C57BL6 mice for a period of 12 weeks

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