Wild blueberry proanthocyanidins shape distinct gut microbiota profile and influence glucose homeostasis and intestinal phenotypes in high-fat high-sucrose fed mice

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.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 . However, wild blueberry has a complex profile of bioactive polyphenols; in addition to anthocyanins, it contains chlorogenic acid, and oligomers and polymers of flavan-3-ols, such as proanthocyanidins (PACs) 5 . Interestingly, there are increased evidences showing that PACs can attenuate the progression of metabolic syndrome, including type 2 diabetes and obesity 6 . Pre-clinical studies have suggested different mechanisms by Figure 3. Wild blueberry polyphenolic fractions restore the mucus thickness and polymeric PACs-rich fraction significantly stimulated mucin-secreting goblet cells number in HFHS-fed mouse colon. The effect of HFHS-diet and the supplementation with WBE and BPF: anthocyanin and phenolic acids (F1), oligomeric PACs, phenolic acids and flavonols (F2) and polymeric PACs (F3) were studied in mouse colon morphology. A combination of Alcian Blue and periodic acid-Schiff...

Polyphenol-induced improvements in glucose metabolism are associated with bile acid signaling to intestinal farnesoid X receptor

“… 47 Rats supplemented with wild blueberry PACs showed increased colonic mucus thickness but no difference in mucin gene expression, which is consistent with mucins being regulated mainly at the post-translational level. 48 49 In agreement, GP supplementation has consistently shown no increase in Muc2 or Muc3 gene expression; however, mucus thickness was not directly investigated in the present study. 1 4 A. muciniphila has generally been associated with decreased gut inflammation and improved health outcomes.…”

Whole Blueberry and Isolated Polyphenol-Rich Fractions Modulate Specific Gut Microbes in an In Vitro Colon Model and in a Pilot Study in Human Consumers

“…Importantly, in older age groups anthocyanins appear to lower the risk of cognitive decline [32]. However, there is a lack of human studies investigating the consumption of polyphenol-rich berries, metabolic improvement, and the microbiota, with the majority of relevant data derived from animal studies [27,[89][90][91][92]. Importantly, we recognize critics of FRAP assays and that, according to the literature, more oxidative damage markers should be added to allow robust conclusions to be drawn [88].…”

Select Polyphenol-Rich Berry Consumption to Defer or Deter Diabetes and Diabetes-Related Complications

“…The BlB-derived anthocyanins also improved the IMBD restoration by decreasing the population of E. coli [ 33 ]. More recently, Rodríguez-Daza and Daoust [ 34 ] also witnessed that BlB-derived proanthocyanidins did not significantly improve the dysbiosis symbolic Firmicutes:Bacteroidetes ratio, but its supplementation did improve the population of genera (Akkermansia, Adlercreutzia, an unknown genus of order Clostridiales, Peptostreptococcaceae, and Ruminococcaceae) considered responsible for the maintenance and restoration of the colon mucosal barrier. The health promoting role of BlB and its byproducts can be explained further by a comprehensive metabolite profile for BlB/BlBE [ 10 , 35 , 36 , 37 , 38 , 39 ] and is shown in Table 2 .…”