Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice

Abstract

Blueberry consumption can prevent obesity-linked metabolic diseases, and it has been proposed that the polyphenol content of blueberries may contribute to these effects. Polyphenols have been shown to favorably impact metabolic health, but the role of specific polyphenol classes and whether the gut microbiota is linked to these effects remain unclear. We aimed to evaluate the impact of whole blueberry powder and blueberry polyphenols on the development of obesity and insulin resistance and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Sixty-eight C57BL/6 male mice were assigned to one of the following diets for 12 wk: balanced diet (Chow); high-fat, high-sucrose diet (HFHS); or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT)-rich extract, or proanthocyanidin (PAC)-rich extract. After 8 wk, mice were housed in metabolic cages, and an oral glucose tolerance test (OGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups biweekly for 8 wk, followed by an OGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC- and ANT-treated mice showed improved insulin responses during OGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity and that at least part of these beneficial effects are explained by modulation of the gut microbiota.

Dietary fat and low fiber in purified diets differently impact the gut-liver axis to promote obesity-linked metabolic impairments

“…Intriguingly, fecal relative abundance of Akkermansia did not discriminate mice fed a LF diet from HF-fed counterparts, although this bacterium was shown to be associated with a healthy phenotype (81-83). While we previously reported the blooming of Akkermansia following treatments of HF-fed animals with various polyphenolic prebiotic extracts that also improved metabolic phenotypes, we rarely found a difference in Akkermansia's relative abundance between HF-fed mice and their chow or LF-fed counterparts (17,(84)(85)(86)(87). This was also reported by other groups (8,88).…”

“…Shannon/Simpson indices (8,17,(84)(85)(86)(87)(88). In the present study, we observed a dramatic decrease of α-diversity in mice fed purified diets as compared to chow-fed mice but only a trend was seen between LF-and HF-fed mice.…”

Blueberry as an Attractive Functional Fruit to Prevent (Pre)Diabetes Progression

“…In vivo animal studies have showed that BB reduced the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in both mouse models of liver injury but also in obese and insulin resistant animal models [ 32 , 151 ]. Conversely, despite changes in lipid peroxidation in the liver, the hepatic TGs accumulation and serum AST and ALT levels were not altered following the administration of whole blueberry powder or polyphenolic-rich extracts in diet-induced obesity and insulin resistant mice [ 152 ]. Interestingly, authors found that the improved metabolic outcomes were only exhibited in obese insulin resistant animals supplemented with BB polyphenol-rich fractions and no improvements were found in mice fed high-fat high-sucrose diet plus whole BB powder, suggesting that the metabolic benefits are a result of specific classes of polyphenols isolated from the whole fruit.…”

Modulation of the host microbiome by black raspberries or their components and the therapeutic implications in cancer

“…They have been demonstrated to both prevent and treat a number of cancers including those of the gastrointestinal tract (Harris et al., 2001; Kuntz, Kunz, & Rudloff, 2017; Peiffer et al., 2014). It is thought that these polyphenols are released from BRB by microbes in the gut and further that once released AC modulate the flora that populates the tissue (Morissette et al., 2020; Peng et al., 2020; Wang et al., 2020). Thus a positive feedback loop occurs in which the bacteria increase AC concentrations within the gut, which then further selects for these microbes to propagate.…”