The impact of Bergamot Polyphenolic Fraction on microbiota in metabolic syndrome

Metabolic syndrome (MetS) represents a set of clinical characteristics that includes visceral adiposity, insulin resistance, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) and hypertension, which is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD).

The pathogenesis of MetS involves both genetic and acquired factors triggering oxidative stress, cellular dysfunction and systemic inflammation process mainly responsible for the pathophysiological mechanism. In recent years, gut dysbiosis and alterations of intestinal microbiota occurring in individuals with MetS has gained importance due to the relationship between the release of endotoxins in the bloodstream and increased risk of cardiovascular diseases. However, at present, it remains underdiagnosed and undertreated.

However, emerging evidence suggests a potential protective role of bergamot extracts – in particular, bergamot flavonoids – in the management of different features of MetS, induced by their pleiotropic antioxidative, anti-inflammatory, and lipid-lowering effects. In particular, evidence exists that the gut microbiota contributes to the alterations of lipid metabolism associated with a high-fat diet (HFD). Moreover, the gut microbiota has been found to modulate the metabolism and absorption of dietary lipids, thereby affecting the formation of lipoproteins occurring at the intestinal level as well as systemically, though the pathophysiological implication of altered microbiota composition in HFD and its role in the development of atherosclerotic vascular disease (ATVD) remain to be better clarified.

Recently, evidence has been collected indicating that supplementation with natural polyphenols and fibres accounts for an improvement of HFD-associated intestinal dysbiosis, thereby leading to improved lipidaemic profile. This study aimed to investigate the protective effect of a bergamot polyphenolic fraction (BPF) containing 40-48% polyphenols enriched with albedo and pulp-derived micronized fibres (BMF) in the gut microbiota of HFD-induced dyslipidaemia. In particular, rats that received an HFD for four weeks showed a significant increase in plasma cholesterol, triglycerides and plasma glucose compared to a normal-fat diet (NFD) group. This effect was accompanied by body weight increase and alteration of lipoprotein size and concentration, followed by high levels of MDA, a biomarker of lipid peroxidation.

Administration of a combination of BPF^® plus BMF (50/50%) resulted in a significant reduction in alterations of the metabolic parameters found in HFD-fed rats, an effect associated with increased size of lipoproteins. Furthermore, the effect of BPF^® plus BMF treatment on metabolic balance and lipoprotein size re-arrangement was associated with reduced gut-derived lipopolysaccharide (LPS) levels, an effect subsequent to improved gut microbiota as expressed by modulation of the Gram-negative bacteria Proteobacteria, as well as Firmicutes and Bacteroidetes. These data have been confirmed in obese individuals.

This suggests that nutraceutical supplementation of HFD-fed rats with BPF alone or in combination products leads to restored gut microbiota, an effect associated with lipoprotein size, re-arrangement, and better lipidaemic and metabolic profiles.