Anthocyanins protect the gastrointestinal tract from high fat diet-induced alterations in redox signaling, barrier integrity and dysbiosis

Abstract

The gastrointestinal (GI) tract can play a critical role in the development of pathologies associated with overeating, overweight and obesity. We previously observed that supplementation with anthocyanins (AC) (particularly glycosides of cyanidin and delphinidin) mitigated high fat diet (HFD)-induced development of obesity, dyslipidemia, insulin resistance and steatosis in C57BL/6J mice. This paper investigated whether these beneficial effects could be related to AC capacity to sustain intestinal monolayer integrity, prevent endotoxemia, and HFD-associated dysbiosis. The involvement of redox-related mechanisms were further investigated in Caco-2 cell monolayers. Consumption of a HFD for 14 weeks caused intestinal permeabilization and endotoxemia, which were associated with a decreased ileum expression of tight junction (TJ) proteins (occludin, ZO-1 and claudin-1), increased expression of NADPH oxidase (NOX1 and NOX4) and NOS2 and oxidative stress, and activation of redox sensitive signals (NF-κB and ERK1/2) that regulate TJ dynamics. AC supplementation mitigated all these events and increased GLP-2 levels, the intestinal hormone that upregulates TJ protein expression. AC also prevented, in vitro , tumor necrosis factor alpha-induced Caco-2 monolayer permeabilization, NOX1/4 upregulation, oxidative stress, and NF-κB and ERK activation. HFD-induced obesity in mice caused dysbiosis and affected the levels and secretion of MUC2, a mucin that participates in intestinal cell barrier protection and immune response. AC supplementation restored microbiota composition and MUC2 levels and distribution in HFD-fed mice. Thus, AC, particularly delphinidin and cyanidin, can preserve GI physiology in HFD-induced obesity in part through redox-regulated mechanisms. This can in part explain AC capacity to mitigate pathologies, i.e. insulin resistance and steatosis, associated with HFD-associated obesity.

Lonicera caerulea L. Polyphenols Alleviate Oxidative Stress‐Induced Intestinal Environment Imbalance and Lipopolysaccharide‐Induced Liver Injury in HFD‐Fed Rats by Regulating the Nrf2/HO‐1/NQO1 and MAPK Pathways

“…The upregulated claudin‐2 expression levels and the downregulated GLP‐2 and occludin expression levels are important for restoring the intestinal barrier function. [ 41‐43 ] GLP‐2 is reported to be a hormone that is present in the intestinal epithelial cells. The expression level of GLP‐2 is positively correlated with mucin secreted by the intestinal goblet cells.…”

“…The expression level of GLP‐2 is positively correlated with mucin secreted by the intestinal goblet cells. [ 41 ] Additionally, claudin‐2 can bind with water and form Na + transport channels, which increases the permeability of the intestinal barrier. Subsequently, this results in an enhanced cytokine response and exacerbation of intestinal tissue damage.…”

Dietary Supplementation of Black Rice Anthocyanin Extract Regulates Cholesterol Metabolism and Improves Gut Microbiota Dysbiosis in C57BL/6J Mice Fed a High‐Fat and Cholesterol Diet

“…[ 12 ] Lots of studies illustrated that supplementing the diet with black rice anthocyanin extract (BRAE) attenuated HCD‐induced development of obesity, hypercholesterolemia, hepatic steatosis, and atherosclerosis. [ 13,14 ] However, it is still unclear how supplementation of BRAE affects gut microbiota and the detailed mechanism that affects hypercholesterolemia as well as whether the gut microbiota homeostasis was indispensable for its protective roles of BRAE.…”

Petunidin-Based Anthocyanin Relieves Oxygen Stress in Lactobacillus plantarum ST-III

“…As far as we are acknowledged, it is the first in vitro study on the interaction between probiotics and ACNs. Oxygen stress relief observed in this study might provide an explanation for ACN-induced increase of Lactobacillus, Bifidobacterium (Chen et al, 2018;Peng et al, 2019), and other anaerobes such as Akkermansia (Cremonini et al, 2019) in intestinal microbiota. Meanwhile, the TRX system is a key component in the antioxidant system widely distributed in lactic acid bacteria, and the enhancement of the TRX system by ACN implies its potential in growth improvement of other oxygen-sensitive probiotics.…”