Negative changes to gut microbial composition have been associated with a variety of metabolic events, including an increase in adiposity, dyslipidemia and type 2 diabetes mellitus (T2DM).¹ Disruption of the microbiome reduces short-chain fatty acid (SCFA) production and leads to increased intestinal permeability. This creates a localised, low-grade state of inflammation and increased lipopolysaccharide (LPS) production and translocation. Consequently, this results in ongoing systemic effects including the disruption of normal glycaemic function,^2,3 promoting the development of T2DM, metabolic syndrome (MetS) and obesity.²

Polyphenols are well known for their beneficial effects on metabolic parameters,⁴ however, they are now recognised to have significant prebiotic activity, modifying gut microbiota, compounding their beneficial systemic effects (Figure 1).^5,6 Polyphenols promote the growth of core bacterial genera, increase SCFA production and contribute to microbial diversity,⁵ which reduces mucosal inflammation and improves mucosal integrity. Of particular importance in metabolic disorders are cocoa and red dragon fruit polyphenols.

CAPTION: Figure 1. Impact of diet on the gut microbiome and human health.⁶

One more piece of chocolate…

Cocoa polyphenols interact bidirectionally with the intestinal microbiota.⁷ Five to ten percent of polyphenols are absorbed in the small intestine, with the remaining 90% to 95% reaching the colon, where they undergo extensive microbial fermentation.⁸ This produces bioavailable secondary metabolites that influence the intestinal microbiome exerting systemic effects including improved endothelial function and reduced lipid deposition, insulin resistance, blood pressure and inflammation.⁷

Several clinical trials have demonstrated cocoa polyphenols to improve markers of metabolic control. A 2021 meta-analysis of eight randomised, controlled trials involving 433 participants investigated the effects of cocoa consumption on lipid profiles, glycemia and blood pressure control in diabetic patients. The results revealed a significant reduction in low-density lipoprotein (LDL) cholesterol and fasting blood glucose concentrations.⁹ In a separate meta-analysis of 42 randomised controlled trials, consumption of cocoa revealed an improvement in insulin sensitivity associated with a decrease in serum insulin.¹⁰ Studies also suggest cocoa-related polyphenol intake may result in reduced appetite and body weight, however, this effect requires further investigation.¹¹

Additionally, a randomised, controlled, double-blind, crossover intervention study found cocoa to reduce total plasma cholesterol (TC) and triglycerides (TGs), increase SCFA production (lactate and acetate) and reduce plasma c-reactive protein (CRP).⁸ While a randomised controlled trial conducted in healthy subjects given 500 mg/d of polyphenols for 15 days found cocoa to lower levels of insulin resistance.¹²

Good fortune from the red dragon

Oligosaccharides from red dragon fruit have demonstrated prebiotic properties, increasing the growth of Lactobacillus and Bifidobacterium species.¹³ However, it is its betacyanin content that has been shown to decrease the ratio of Firmicutes and Bacteroidetes, and increases the relative abundance of Akkermansia muciniphila (A. muciniphila),¹⁴ a mucin-degrading bacteria that has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders.¹⁵

In healthy populations, A. muciniphila is present at normal levels, however, it decreases in patients with active inflammation or in those who suffer from diabetes, gastrointestinal diseases or obesity.¹⁶ A. muciniphila has strong anti-inflammatory properties and promotes improved intestinal integrity, reducing the absorption and translocation of LPS, a causative mechanism for metabolic-induced obesity.¹⁷ A. muciniphila has been found to impact several metabolic parameters including the clearance of TGs and postprandial chylomicrons, improve glucose tolerance, and trimethylamine N-oxide (TMOA), which is strongly associated with the development of cardiovascular disease (CVD).¹⁸ The antioxidant action of polyphenols also protects A. muciphiila, which is vulnerable to attack by free radicals.¹⁹

A systematic review and meta-analysis evaluating the effects of red dragon fruit on glycaemic control in prediabetics and patients with T2DM included four randomised, controlled trials involving 36 prediabetic patients and 109 T2DM patients. In prediabetic patients, red dragon fruit demonstrated a reduction in fasting postprandial glucose levels. While in T2DM no significant effect was found, though there was a trend towards greater blood glucose reductions.²⁰

In another trial evaluating the effects of red dragon fruit powder on blood glucose and lipid profiles in prediabetic patients, 36 participants were divided into either treatment groups (receiving either 60 g/d, 80 g/d or 100 g/d) or the control group. The results showed each treatment group had a reduction of plasma blood glucose levels, plasma lipid profiles, TC, TGs, and LDL. The results were most significant in the 100 g/d treatment group.²⁰

A novel approach to metabolic disorders

The link between the microbiome and metabolic heath has been firmly established, as have the benefits of prebiotics on gut microbial composition. As prebiotics, cocoa and red dragon fruit polyphenols promote the growth of beneficial intestinal populations, most notably A. muciniphila, which has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders.³ Evidence supports the benefits of both cocoa and red dragon fruit polyphenols on a number of metabolic markers resulting in improved insulin signalling and lipid profiles. As such, a combination of cocoa and red dragon fruit may be used as a novel therapeutic to manage metabolic disorders such as T2DM and MetS.

References:

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