Abstract

Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases. However, the health contribution and mechanisms of action of polyphenols depend on their type and structure. Here, we evaluated the effects of a wild blueberry polyphenolic extract (WBE) (Vaccinium angustifolium Aiton) on cardiometabolic parameters, gut microbiota composition and gut epithelium histology of high-fat high-sucrose (HFHS) diet-induced obese mice and determined which constitutive polyphenolic fractions (BPF) was responsible for the observed effects. To do so, the whole extract was separated in three fractions, F1) Anthocyanins and phenolic acids, F2) oligomeric proanthocyanidins (PACs), phenolic acids and flavonols (PACs degree of polymerization DP < 4), and F3) PACs polymers (PACs DP > 4) and supplied at their respective concentration in the whole extract. After 8 weeks, WBE reduced OGTT AUC by 18.3% compared to the HFHS treated rodents and the F3 fraction contributed the most to this effect. The anthocyanin rich F1 fraction did not reproduce this response. WBE and the BPF restored the colonic mucus layer. Particularly, the polymeric PACs-rich F3 fraction increased the mucin-secreting goblet cells number. WBE caused a significant 2-fold higher proportion of Adlercreutzia equolifaciens whereas oligomeric PACs-rich F2 fraction increased by 2.5-fold the proportion of Akkermansia muciniphila. This study reveals the key role of WBE PACs in modulating the gut microbiota and restoring colonic epithelial mucus layer, providing a suitable ecological niche for mucosa-associated symbiotic bacteria, which may be crucial in triggering health effects of blueberry polyphenols.

Highlights

  • Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases

  • Wild blueberries (Vaccinium angustifolium Aiton) are recognized as a rich source of bioactive phenolic compounds, the consumption of which has been associated with the attenuation of metabolic disorders through its beneficial action on glucose homeostasis and the reduction the oxidative stress and intestinal inflammation[1,2]

  • We investigated the impact of the oral administration of wild blueberry extract or three polyphenolic fractions on the diet-induced glucose intolerance, insulin sensitivity and on the gut microbiota composition, as well as on intestinal epithelium histology

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Summary

Introduction

Blueberries are a rich source of polyphenols, widely studied for the prevention or attenuation of metabolic diseases. Wild blueberries (Vaccinium angustifolium Aiton) are recognized as a rich source of bioactive phenolic compounds, the consumption of which has been associated with the attenuation of metabolic disorders through its beneficial action on glucose homeostasis and the reduction the oxidative stress and intestinal inflammation[1,2] Until now, these positive effects have predominantly been attributed to flavonoids and in particular to anthocyanins[3,4]. A highbush blueberry polyphenolic fraction and an anthocyanin-enriched fraction were found to attenuate gut barrier dysfunction induced by E. coli in a model of Caco-2 epithelial cell culture[21] Whilst those findings have been obtained using different methodologies and model systems, together they provide strong evidences to suggest that wild blueberry polyphenols can selectively modulate the gut microbiota composition and prevent intestinal and metabolic obesity-associated disorders. We investigated the impact of the oral administration of wild blueberry extract (hydro-ethanolic extract, WBE) or three polyphenolic fractions (anthocyanins and phenolic acids, oligomeric PACs with flavonols and phenolic acids, and PACs polymers in the respective amounts found in the whole blueberry extract) on the diet-induced glucose intolerance, insulin sensitivity and on the gut microbiota composition, as well as on intestinal epithelium histology

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